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 Blood, 15 April 2008, Vol. 111, No. 8, pp. 4403-4412.
Prepublished online as a Blood First Edition Paper on February 6, 2008; DOI 10.1182/blood-2007-06-097287.

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TRANSPLANTATION

CCL8 is a potential molecular candidate for the diagnosis of graft-versus-host disease

Tsukasa Hori1,2, Yasuyoshi Naishiro1, Hitoshi Sohma1, Nobuhiro Suzuki2, Naoki Hatakeyama2, Masaki Yamamoto1,2, Tomoko Sonoda3, Yuka Mizue4, Kohzoh Imai, Hiroyuki Tsutsumi2, and Yasuo Kokai1

1 Department of Biomedical Engineering, 2 Department of Pediatrics, and 3 Department of Public Health, Sapporo Medical University School of Medicine, Sapporo; and 4 Sapporo ImmunoDiagnostic Laboratory, Sapporo, Japan

Although graft-versus-host disease (GVHD) is a life-threatening complication of hematopoietic stem-cell transplantation (HSCT), its current diagnosis depends mainly on clinical manifestations and invasive biopsies. Specific biomarkers for GVHD would facilitate early and accurate recognition of this grave condition. Using proteomics, we screened for plasma proteins specific for GVHD in a mouse model. One peak with 8972-Da molecular mass (m/z) retained a discriminatory value in 2 diagnostic groups (GVHD and normal controls) with increased expression in the disease and decreased expression during cyclosporin A treatment, and was barely detectable in syngeneic transplantation. Purification and mass analysis identified this molecule as CCL8, a member of a large chemokine family. In human samples, the serum concentration of CCL8 correlated closely with GVHD severity. All non-GVHD samples contained less than 48 pg/mL (mean ± SE: 22.5 ± 5.5 pg/mL, range: 12.6-48.0 pg/mL, n = 7). In sharp contrast, CCL8 was highly up-regulated in GVHD sera ranging from 52.0 to 333.6 pg/mL (mean ± SE: 165.0 ± 39.8 pg/mL, n = 7). Strikingly, 2 patients with severe fatal GVHD had extremely high levels of CCL8 (333.6 and 290.4 pg/mL. CCL8 is a promising specific serum marker for the early and accurate diagnosis of GVHD.


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